Discovery of mitochondrion-targeting copper(II)-plumbagin and -bipyridine complexes as chemodynamic therapy agents with enhanced antitumor activity.

Four copper(II)-plumbagin and -bipyridine complexes (Cu1-Cu4) were synthesized as chemodynamic therapy agents with enhanced antitumor activity. As lipophilic and positively charged compounds, Cu1-Cu4 were preferentially accumulated in mitochondria and activated the mitochondrial apoptosis pathway. Mechanistic studies showed that Cu1-Cu4 reacted with GSH to reduce Cu ions to Cu ions, catalyzed the formation of toxic hydroxyl radicals (˙OH) from hydrogen peroxide (HO) through a Fenton-like reaction, induced mitochondrial dysfunction, and activated caspase-9/3, which eventually led to apoptosis.

Copper(II) complexes with plumbagin and bipyridines target mitochondria for enhanced chemodynamic cancer therapy.

The combination of mitochondrial targeting and chemodynamic therapy is a promising anti-cancer strategy. Three mitochondria targeting copper(II) complexes (Cu1-Cu3) with plumbagin and bipyridine ligands for enhanced chemodynamic therapy were synthesized and characterized. Their anti-proliferative activity to HeLa cells was higher than that of cisplatin, and their toxicity to normal cells was low.

Platinum-Based Mcl-1 Inhibitor Targeting Mitochondria Achieves Enhanced Antitumor Activity as a Single Agent or in Combination with ABT-199.

Discovery of small molecule inhibitors targeting Mcl-1 (Myeloid cell leukemia 1) confronts many challenges. Based on the fact that Mcl-1 is mainly localized in mitochondria, we propose a new strategy of targeting mitochondria to improve the binding efficiency of Mcl-1 inhibitors. We report the discovery of complex , the first mitochondrial targeting platinum-based inhibitor of Mcl-1, which selectively binds to Mcl-1 with high binding affinity.

[Minimally invasive osteotomy and manual reduction for hallux valgus].

Objective: To explore clinical effects of minimally invasive osteotomy and manual reduction in treating hallux valgus.

Methods: From January 2018 to May 2019, 31 patients (42 feet) with hallux valgus were treated with minimally invasive osteotomy and manual reduction, including 3 males and 28 females aged from 18 to 76 years old with an average of (50.1± 4.

Polymer-drug conjugates: present state of play and future perspectives.

Polymer conjugation is an efficient approach to improve therapeutic properties of drugs and biological agents. Since the first synthetic polymer-drug conjugate entered clinical trials in 1994, this technology has undergone notable development for the introduction and study of novel polymers and for the progress in the biological rationale for designing conjugates. Not surprisingly, new polymers, in addition to the best known polyethylene glycol, poly[N-(2-hydroxypropyl)methacrylamide], are continuously conjugated with drugs to achieve biodegradable, stimuli-sensitive and targeted systems in an attempt to prolong blood circulation times and enhance drug concentrations at the intended site of action.